Crystal structure of Ultralente - a microcrystalline insulin suspension

DOI: 10.1002/prot.22213

Authors: Armin Wagner (Swiss Light Source; Diamond Light Source; Novo Nordisk A/S) , Joachim Diez (Swiss Light Source) , Clemens Schulze-Briese (Swiss Light Source) , Gerd Schluckebier (Novo Nordisk)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Proteins: Structure, Function, And Bioinformatics , VOL 74 (4) , PAGES 1018-1027

State: Published (Approved)
Published: June 2008

Abstract: Ultralente insulin has been one of the commercially most important insulin preparations in diabetes treatment over the last 50 years. It is a suspension of insulin microcrystals which dissolve slowly following subcutaneous injection. Because of the small crystal size of about 25 × 25 × 5 ?m3 the atomic structure has been elusive until now. Here we present the crystal structures from Ultralente and their precursor microcrystals from the industrial manufacturing process. During this process insulin undergoes a conformational change within the microcrystals. Both structures show canonical folding of the insulin molecules but exhibit a number of new features when compared with other insulin structures. Surprisingly, we found that the Ultralente crystals bind the conservation agent methylparaben, which slows down dissolution of the crystals and thus contributes to the long duration of action.

Journal Keywords: Microcrystals; Microfocus Beam; Insulin

Diamond Keywords: Diabetes

Subject Areas: Biology and Bio-materials, Medicine

Facility: X06SA at SLS

Added On: 19/08/2009 23:07

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags: